Background
CML is usually classified in chronic phase (CP), accelerated phase (AP) and/or Blast phase (BP). Studies have described another provisional entity as Preleukemic phase of CML which precedes CP and is without leukocytosis and blood features of CP phase of CML. Here we will present a case of metastatic prostate cancer, where next-generation sequencing showed BCR-ABL1 but no overt leukocytosis and then later developed clinical CML after 11 months.
Case Presentation
Our patient was 87-yr-old male with history of metastatic prostate cancer, who presented with elevated PSA levels and new bony metastasis. He underwent next-generation-sequencing (foundation one liquid cdx) in April 2022. It did not show reportable alterations related to prostate cancer but BCR-ABL1 (p210) fusion was detected. It also showed ASXL1-S846fs5 and TET2-Q1548 that are also markers of clonal hematopoiesis. In March 2023 (11 months after the finding of BCR-ABL1), he developed asymptomatic leukocytosis, Workup showed BCR-ABL1(210) of 44% in peripheral blood and bone marrow showed 9% blasts. He was started on Imatinib after shared decision-making and considering the toxicity profile and comorbidities. He followed up regularly with improvement in leukocytosis.
Discussion
The diagnosis of CML is first suspected by typical findings in blood and/or bone marrow and then confirmed by presence of Philadelphia chromosome. Along with chronic and accelerated phases, there is another term described in few cases called “preleukemic or smoldering or aleukemic phase.” This is not a wellestablished term but mostly defined as normal leukocyte count with presence of BCR/ABL1 fusion gene/ ph chromosome. Preleukemic phase of CML is mostly underdiagnosed or misdiagnosed. Our case is unique in that BCR/ABL1 fusion was detected incidentally on next-generation sequencing and patient progressed to chronic phase of CML 11 months later. Upon literature review, few case reports and case series documenting aleukemic/preleukemic phase of CML but timing from the appearance of BCR/ABL1 mutation to actual development to leukocytosis is not well documented. Especially in the era of NGS testing, patients with incidental BCR-ABL1 should be evaluated further irrespective of normal WBC. Further studies need to be done to recognize this early and decrease the delay in treatment.
